Comprehensive Molecular Profiling Of The B7 Family In Gastrointestinal Cancer

objective: B7 family has been identified as co-stimulatory or co-inhibitory molecules on T-cell response and plays an important role in tumor mortality and malignancy.In this study,the expression pattern of B7 family in gastrointestinal(GI)cancer was examined.Its upstream regulating mechanism,downstream targets and association with clinical parameters were also studied.Combing with related clinical tissue sample to investigate the key genes dysregulated expression status in stomach cancer patients,and analysis the clinical influence of the gene expression in different disease status.Methods: Collecting the high-throughput sequencing data from public database TCGA,filtering and adding the genetic expression in different types of gastrointestinal cancer,and normalized the expression data with uniform method.The expression level of B7 members was analyzed by FIREHOUSE.The gene mutation,DNA methylation,association with clinical parameters and downstream network of B7 members were analyzed in cBioportal.The mutation frequency was analyzed by Catalogue of Somatic Mutations in Cancer(COSMIC)analysis.The phylogenetic tree was constructed in MEGA7.The interaction protein domain analysis was performed by Pfam 31.0.Collecting the Postoperative patients with gastric cancer tumor tissues and normal and chemical staining with the B7 family genes antibody,then analyzed by professional software to identify the different expression level.Results: Differential expression of B7 family molecules was detected in different kinds of GI cancer.High-frequency gene alteration was found in tumor samples.There was negative correlation of promoter methylation and mRNA expression of B7 family members in tumor samples,suggesting the epigenetic basis of B7 family gene deregulation in GI cancer.The overexpression of B7-H1 in pancreatic cancer,B7-H5 in esophageal cancer and B7-H6 in liver cancer were significantly associated with worse overall survival.Finally,by network analysis,we identified some potential interacting proteins for B7-1/2 and B7-H1/DC.Through the immunohistochemical staining,we found that B7 family gene expression in stomach cancer tissues were higher than normal sample.Conclusion: Overall,our study suggested that B7 member deregulation was strongly involved in GI cancer tumorigenesis.Especially,gastrointestinal cancer patients overall survival,tumor malignance statue and tumorigenesis related signaling pathway alteration were closely associated with B7 family dysregulation.Moreover,B7 family genetic mutation may be a meaningful research orientation of the gastrointestinal cancer targeted immune therapy in the future.